Tadashi Kotake

Dendritic Cell-Based Immunotherapy of Renal Cell Carcinoma

Dendritic cells potently stimulate antigen-specific immune responses and recent data indicate that they are also capable of eliciting antitumor immune responses. We are performing a pilot study which tests the safety and efficacy of antigen-loaded, cultured blood dendritic cells in patients with metastatic renal cell carcinoma. Dendritic cells are simultaneously pulsed with lysate from autologous tumor cells and with the immunogenic protein keyhole limpet hemocyanin. During the pulse, the cells are activated with a combination of tumor necrosis factor-alpha and prostaglandin E2. Patients receive 5-10 X 10(6) dendritic cells per intravenous infusion and up to six infusions at monthly intervals. The first results demonstrate that this treatment modality is very well tolerated and can be associated with strong immunological and clinical responses. The present article discusses the importance of dendritic cell maturation and the role of helper antigens in dendritic cell-based immunotherapy.

Oral Calcium Supplement Decreases Urinary Oxalate Excretion in Patients with Enteric Hyperoxaluria

We studied the effect of oral calcium supplementation in patients with enteric hyperoxaluria. Three patients with renal stone events following ileal resection were given oral calcium supplement. One of the three patients was put on a low-fat diet. The treatment reduced urinary oxalate excretion to the normal range. Subsequently, 2 patients reduced the dose of calcium supplementation at their own discretion and consequently developed renal stones again together with hyperoxaluria. Based on these observations, we believe that an adequate dose of calcium can normalize urinary oxalate excretion.

Results Obtained from Microsurgical Therapy of Varicocele

The microsurgical method of varicocelectomy was performed in 56 patients. In 25 cases the procedure was done because of scrotal symptoms and in 31 cases as a treatment for infertility. Complete regression of varicosities was observed in all the cases including 2 recurrent ones. The conception rate was 56% in the infertility patients excluding azoospermic and severe oligozoospermic ones. This microsurgical method has a good success rate and is also quite satisfactory in terms of its pregnancy rate.

HIGH DOSE HOOK EFFECT IN SERUM TOTAL AND FREE PROSTATE SPECIFIC ANTIGEN IN A PATIENT WITH METASTATIC PROSTATE CANCER

High dose hook effect is a phenomenon in which samples with extremely high analyte concentrations may paradoxically produce a lower response than expected in an immunoradiometric assay. This effect has been observed while measuring serum prostate specific antigen (PSA) with a Tandem R assay (Hybritech Beckman-Coulter Corp., San Diego, California). 1 We report the occurrence of a hook effect while measuring total and free PSA in a patient with metastatic prostate cancer. CASE REPORT An 85-year-old man was referred to us for paraplegia and suspected bone metastasis of prostate cancer. Serum total and free PSA measured with a Tandem R assay before digital rectal examination was 11 and 0.5 ng./ml., respectively, and g-seminoprotein measured with an Eiken kit (Eiken, Tokyo, Japan) was 1,800 ng./ml. Digital rectal examination revealed enlargement of the left lobe with no extension beyond the prostate. Bone scintigraphy suggested metastases to the pelvis with the extent of disease score 2. Pathological examination confirmed the diagnosis of adenocarcinoma of the prostate (Gleason 4 to 5). Orchiectomy was performed simultaneously. Because we thought total PSA of 11 ng./ml. was falsely low, repeat analysis after dilution was performed. After 1,0003 dilution total and free PSA concentrations were 26,000 and 1,050 ng./ml., respectively. We determined that the hook effect had occurred in this case. Although total and free PSA values decreased, the patient died of prostate cancer 2 months after orchiectomy. DISCUSSION

Clinical and biochemical features of uric acid nephrolithiasis

A clinical investigation was carried out on patients with uric acid stones in order to study the frequency and pathogenesis of uric acid nephrolithiasis. Of 652 patients with stones in the upper urinary tract in whom the stone composition could be examined, 36 patients and uric acid stones (5.5%). The male to female ratio was 11:1. The average age of the 33 male subjects was 49 +/- 11 years (mean +/- SD), and the 3 females were 22, 37 and 42 years old, respectively. Two of the females showed hypouricemia. With regard to stone composition, pure uric acid stones were present in 26 cases (72%), a mixed uric acid and calcium oxalate stones were found in 6 cases (17%), both pure uric acid and mixed uric acid and calcium oxalate stones were observed in 3 cases (8%), and a mixed uric acid and sodium acid urate stone in 1 (3%). Biochemical studies on male patients showed that the blood uric acid level was higher in the uric acid stone group and the pure uric acid stone group compared to the calcium stone group. The blood uric acid levels of the former 2 groups did not differ from the control group. With respect to urine chemistry, the excretion of calcium in the uric acid stone group was significantly lower than that in the control group. In the uric acid stone group and the pure uric acid stone group the excretion of calcium tended to be lower than that in the calcium stone group. The amounts of oxalic acid excreted in the uric acid stone group and in the pure uric acid stone group were low compared to the calcium stone group. Oxalic acid elimination in these 2 groups did not differ from the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

The long-term outcome of cystinuria in Japan

Recurrence of growth of urinary stone is frequently observed during the clinical course of cystinuria patients. The aim of the present study is to examine the long-term outcome of cystinuria in Japan and clarify the effects of medical treatment on urinary stone. Thirty-one patients with cystinuria who had been followed up longer than 6 months were included. The follow-up period was 6–264 months with a mean of 89.5 months. Stone event was defined as appearance of new stone or radiological evidence of stone growth. All patients were managed with forced hydration and urine alkalization. Twenty-eight patients were treated with administration of thiol such as D-penicillamine or α-mercaptopropionylglycine. Stone events per year ranged from 0 to 1.09 with a median of 0.09. Stone events per patient-year was 0.19 for all patients. The average urinary cystine concentration during treatment in the favorable outcome group (stone events per year < 0.3) was lower that that in the unfavorable outcome group (stone events per year ≥0.3); 221.2 ± 75.2 vs. 303.3 ± 93.5 mg/l, although the difference was not statistically significant. Prognosis of urinary stone in Japanese patients with cystinuria was relatively good with large variation. The medical treatment to reduce urinary cystine concentration would be useful for the management of cystinuria.

Primary Localized Amyloidosis of the Ureter Associated with Osseous Metaplasia

A case of primary localized amyloidosis of the ureter associated with osseous metaplasia, presenting as a calcification on computerized tomography, is reported. We believe this is the second such case to be reported in the world literature. The previous 34 cases of primary amyloidosis of the ureter are reviewed and the clinical presentations and treatments discussed. The difficulties of distinguishing the condition from transitional cell carcinoma of the ureter is emphasized. Surgical treatment should be conservative, if possible.

Effect of Ethyl Icosapentate on Urinary Calcium Excretion in Calcium Oxalate Stone Formers

Buck and co-workers presented the hypothesis that the initiating factor of stone formation triggers the mechanisms for prostaglandin synthesis, resulting in the biochemical abnormalities associated with stone disease. In order to test this hypothesis, we undertook a clinical study with the use of a highly purified preparation of ethyl icosapentate. Ethyl icosapentate (1,800 mg/day) was administered to 57 patients with urinary stones chiefly composed of calcium oxalate for 6 weeks. Urinary calcium in the hypercalciuric patients reduced significantly, but the calcium level in the normocalciuric group did not decrease. Oxalate values did not reduce either in the hypercalciuric patients or in the normocalciuric subjects. No serious side effects were observed.

Usefulness of aspiration cytology in prostate cancer detection.

Aspiration cytology and core needle biopsy were performed in 79 patients who were suspected of having prostate cancer. Aspiration cytology and TURP were done in 77 cases not suspected of the disease. In the former group, they were both positive in 13 cases, aspiration cytology was negative and core needle biopsy positive in 4, and the reverse in 3 cases in whom cancer was confirmed by repeat core biopsy. All of the latter group were judged by aspiration cytology as being benign. Three cancers were detected by TURP. Aspiration cytology is a recommendable method in subjects with suspected prostate cancer.

Comparison of T1c versus T2 prostate cancers in Japanese patients undergoing radical prostatectomy.

In order to examine the characteristics of patients with nonpalpableprostate cancer (T1c cancer) in Japan, patients treated with radicalprostatectomy were compared with those with palpable (T2) cancer.Prostate-specific antigen (PSA) level in patients with T2b disease wassignificantly higher than those with T1c and T2a tumors. At the time ofradical prostatectomy, 78%, 71% and 31% of patients with T1c, T2a, and T2b, respectively, had organ-confined disease. When insignificant cancerwas defined as volume 0.5 ml or less and Gleason score less than 5, only 2 of34 (5.9%) with clinical T1c disease were clinically insignificant. T1c cancerswere clinically significant and clinicopathological features of T1c tumorswere similar to T2a tumors. PSA measurement could detect potentiallycurable prostate cancer.